Coronary artery disease (CAD) results from arteriosclerosis of blood vessels serving the heart. Arteriosclerosis is a hardening and narrowing of the arteries commonly accompanied by a deposition of waxy substance therein. This substance, known as plaque, is made of cholesterol, fatty compounds, calcium, and the blood-clotting material fibrin. Often the arteries of the heart can suddenly become so severely blocked that there is an inadequate blood supply after the blockage, leading to the occurrence of a myocardial infarction or heart attack. Although some heart attacks are caused by such “hard” plaques, many are caused by “soft” or vulnerable plaques. A vulnerable plaque is an inflamed part of an artery that can burst. This can lead to the formation of a blood clot, which can reduce or block the flow of blood.
Soon after a myocardial infarction, the area of cardiac tissue downstream the blockage may suffer damage. The damage is caused by a lack of adequate blood flow, known as ischemia, as the tissue is starved of oxygen and nutrients. Unless the blockage is resolved relatively quickly, the ischemic cells may begin to die. Often, a surgical procedure, such as a Coronary Artery By-Pass Grafting (CABG), is used to graft new blood vessels to the ischemic area to improve circulation. Alternatively, a Percutaneous Transluminal Coronary Angioplasty (PTCA) procedure optionally accompanied by stenting of the blocked vessel is performed to reopen the vessel and maintain blood flow. However, by-passing or reopening of the arteries is sometimes not possible or at least not immediately possible because of limitations of present methodologies, risk to the patient from surgical intervention, or other circumstances. In certain instances, it may be preferable to treat the heart condition by utilizing the cardiac venous system, which generally runs parallel to or adjacent to the coronary arteries.
One therapy for limiting or reducing myocardial damage during or after a heart attack involves a localized delivery of therapeutic agent(s) to the heart tissue. The therapeutic agents include gene therapy agents, which have recently emerged as a powerful approach to treating a variety of diseases. The direct transfer of genetic material into myocardial tissue in vivo has been demonstrated for expressing various proteins. Engineered and stem cell therapies have also shown promise. The therapeutic agents may also include drug agents. The expressed proteins and drug agents may have various therapeutic benefits for improving circulation/angiogenesis, limiting ongoing tissue damage, preventing future tissue damage, repairing damaged tissue, and the like.
The localized delivery of therapeutic agents to a specific treatment site, such as the heart, represents a substantial challenge in the design of delivery systems. An approach to accomplish site-specific drug delivery involves the use of a catheter or like device, which can be advanced through the vasculature and positioned at a treatment site. The catheter provides localized delivery of drug from a location that may be some distance from the treatment site (i.e., outside the body of the patient). For example, a blocked artery may prevent blood from flowing downstream into its corresponding vein. As such, accessing the blockage from the venous direction provides a viable treatment option.
One consideration for catheter design relates to its maneuverability. The advancement of the catheter through the sometimes tortuous vasculature requires a relatively flexible device. A maneuverable catheter may reduce the time and skill needed to advance the apparatus to the treatment site. In addition, a maneuverable catheter may be less likely to contact the vascular tissue during its advancement therefore minimizing trauma to the vessels. Another consideration in the design of catheters used for therapeutic agent delivery relates to those devices used for long-term agent delivery (e.g., several hours to several days, weeks, or months). Long-term therapeutic agent delivery requires that such catheters do not occlude the blood flow for an extended period of time, thereby allowing downstream tissue to receive an adequate blood supply.
Accordingly, it would be desirable to provide a strategy for intravascularly delivering therapeutic agents that would overcome the aforementioned and other limitations.